Clinical Course and the Role of Shiga Toxin–Producing<i>Escherichia coli</i>Infection in the Hemolytic‐Uremic Syndrome in Pediatric Patients, 1997–2000, in Germany and Austria: A Prospective Study

Gerber, Angela; Karch, Helge; Allerberger, Franz; Verweyen, Hege M.; Zimmerhackl, Lothar Bernd

doi:10.1086/341940

Cited by 334 publications

(358 citation statements)

References 39 publications

(65 reference statements)

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“…Atypical HUS is diagnosed in 1 of 10 patients with HUS (40). Although the incidence of complement associated aHUS is not known, one can estimate that the incidence of aHUS is about 1-2:10 6 (41).…”

Section: Discussionmentioning

confidence: 99%

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

Hofer¹,

Janecke

Zimmerhackl³

et al. 2013

Clinical Journal of the American Society of Nephrology

119

108

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SummaryBackground and objectives This study evaluated the relevance of complement factor H (CFH)-related protein (CFHR) 1 deficiency in pediatric patients with atypical hemolytic uremic syndrome (aHUS) by evaluating both the frequency of deletions in CFHR1 and the presence of complement factor H (CFH) antibodies.Design, setting, participants, & measurements A total of 116 patients (mainly from central Europe) and 118 healthy blood donors were included from 2001 to 2012. The presence of CFHR1 gene deletions was determined in 90 pediatric patients with aHUS and 118 controls by an easy, fast, and cheap PCR assay; 100 patients with aHUS and 42 controls were tested for CFH antibodies by ELISA. Questionnaires were administered to evaluate the clinical and laboratory data.Results Homozygous deletion in CFHR1 was detected in 32% of the patients with aHUS tested, compared with 2.5% of controls (P,0.001). CFH antibodies were present in 25% of the patients and none of the controls. CFH antibodies were detected in 82% of patients with homozygous CFHR1 gene deletion and in 6% of patients without. CFH antibody-positive patients with aHUS showed a significantly lower platelet nadir at disease onset and significantly less frequent involvement of the central nervous system than did antibody-negative patients. Antibody-positive patients also received plasma therapy more often.Conclusion Homozygous deletion in CFHR1 is strongly associated with occurrence of CFH antibodies in pediatric patients with aHUS. However, despite this apparent genetic disease predisposition, it cannot be considered an exclusive cause for aHUS. Initial presentation of Shiga toxin-negative HUS with severe thrombocytopenia and no central nervous system complications in pediatric patients is especially suspicious for CFH antibody aHUS.

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Section: Discussionmentioning

confidence: 99%

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

Hofer¹,

Janecke

Zimmerhackl³

et al. 2013

Clinical Journal of the American Society of Nephrology

119

108

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“…Microbiology E. coli O157:H7 is the most commonly involved serotype; recently, other serotypes have also been described. Gerber et al [25] in a prospective study described 394 pediatric patients with HUS. They found that 43% of these children had an E. coli strain other than O157:H7 in their stool: O26: H11/H-(15%), O157:H-(10%), O145: 28/H-(9%), O103/H2/H-(3%) and O111/H8/H (3%).…”

Section: Epidemiologymentioning

confidence: 99%

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

Salvadori

Bertoni²

2013

WJN

112

111

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Hemolytic uremic syndrome (HUS) is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and pathogenetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the complement proteins are clearly involved in all types of thrombotic microangiopathy: typical HUS, atypical HUS and thrombotic thrombocytopenic purpura (TTP). Furthermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic aspects of this rare disease, examining both "traditional therapy" (including plasma therapy, kidney and kidneyliver transplantation) and "new therapies". The latter include anti-Shiga-toxin antibodies and anti-C5 monoclonal antibody "eculizumab". Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purified, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.

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“…The large number of patients who needed simultaneous treatment was challenging, especially on resources, but the initial rate of complications was not unusual. Especially when looking at the published pediatric series from the US [5], Australia [6], Great Britain [7], and Germany [8], it seems that most pediatric patients with STEC O104:H4 HUS had a comparable course compared to historic controls. Two special features compared to the past, however, were the fact that patients were from a high socioeconomic status and that age at presentation was relatively high.…”

Section: Specific Pediatric Details In Comparison To Published Seriesmentioning

confidence: 99%

Outbreak of hemolytic uremic syndrome caused by E. coli O104:H4 in Germany: a pediatric perspective

Kemper

2011

Pediatr Nephrol

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In May-June 2011, an unprecedented outbreak of hemolytic uremic syndrome (HUS) caused by Shiga toxinproducing E. coli (STEC) O104:H4 affected >800 adults, in whom this disorder is usually rarely seen. Over 90 children were also affected in the largest STEC-associated HUS outbreak in children to date. Despite high patient numbers and chronic staff shortages in pediatric institutions, almost all patients were treated locally, mainly because of maximally increased staff input. Epidemiologic features were characterized by relatively high age at presentation, possibly related to the isolated etiologic agent, raw bean sprouts. Fortunately, in children, other clinical features, including neurological complications, dialysis requirement, and short-term outcome, were comparable to previous historical series. Only one child died, compared to 35 adults. Differences in treatment recommendations and approaches between adults and children were noted. Treatment with eculizumab was available, but handled more restrictively in children. Despite treatment differences, children and adult clinical outcomes were comparable, pending a final analysis. In summary the STEC O104:H4 HUS outbreak was challenging for pediatric resources but clinical presentation and complications were comparable to previous experience. Acute outbreak onset made structured approaches to treatments impossible, however, ongoing analysis may provide evidence for improving care of children with STEC HUS.

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Clinical Course and the Role of Shiga Toxin–ProducingEscherichia coliInfection in the Hemolytic‐Uremic Syndrome in Pediatric Patients, 1997–2000, in Germany and Austria: A Prospective Study

Cited by 334 publications

References 39 publications

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

Outbreak of hemolytic uremic syndrome caused by E. coli O104:H4 in Germany: a pediatric perspective

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